Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetic nephropathy, characterised pathologically by glomerulosclerosis, may account for up to 40% of end-stage renal cases. The short-term (within 3 months) streptozotocin- or alloxan-induced rat model is often used but glomerulosclerosis is seldom reported and it is unclear what the primary renal lesions are. Diabetic rats were studied at 1, 3 and 6 months after a single injection of alloxan. Both methacrylate and paraffin-embedded renal sections were obtained and stained with PAS and haematoxylin. A morphometric study was performed with stereological methods to obtain the volumes and lengths or diameters of renal tubules and glomeruli. A key morphological change associated with sustained hyperglycaemia was the accumulation of glycogen granules in about half of the distal tubules and thin segments starting from 1 month after the experiment, which was then extended to about half of the proximal tubules at 6 months. Renal hypertrophy was seen with a 9% increase in the tubule diameter but not in the total length; glomerular morphology was basically unaffected. Further studies are needed to establish whether glomerulosclerosis would occur in longer term and whether this animal model would be appropriate to study the human condition of diabetes mellitus in terms of renal damage.
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PMID:Glycogen accumulation in renal tubules, a key morphological change in the diabetic rat kidney. 1594 46

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.
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PMID:Fibrogenesis in fatty liver associated with obesity and diabetes mellitus type 2. 1784 88

The metabolic syndrome, a complex set of phenotypes typically associated with obesity and diabetes, is an increasing threat to global public health. Fundamentally, the metabolic syndrome is caused by a failure to properly sense and respond to cellular metabolic cues. We studied the role of the cellular metabolic sensor PAS kinase (PASK) in the pathogenesis of metabolic disease by using PASK(-/-) mice. We identified tissue-specific metabolic phenotypes caused by PASK deletion consistent with its role as a metabolic sensor. Specifically, PASK(-/-) mice exhibited impaired glucose-stimulated insulin secretion in pancreatic beta-cells, altered triglyceride storage in liver, and increased metabolic rate in skeletal muscle. Further, PASK deletion caused nearly complete protection from the deleterious effects of a high-fat diet including obesity and insulin resistance. We also demonstrate that these cellular effects, increased rate of oxidative metabolism and ATP production, occur in cultured cells. We therefore hypothesize that PASK acts in a cell-autonomous manner to maintain cellular energy homeostasis and is a potential therapeutic target for metabolic disease.
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PMID:PAS kinase is required for normal cellular energy balance. 1787 7

Metabolic disorders, such as diabetes and obesity, are fundamentally caused by cellular energy imbalance and dysregulation. Therefore, understanding the regulation of cellular fuel and energy metabolism is of great importance to develop effective therapies for metabolic disease. The cellular nutrient and energy sensors, AMPK and TOR, play a key role in maintaining cellular energy homeostasis. Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive protein kinase. In yeast, PAS kinase phosphorylates the enzyme Ugp1 and thereby shifts glucose partitioning toward cell wall glucan synthesis at the expense of glycogen synthesis. Consistent with this function, yeast PAS kinase is activated by both cell integrity stress and growth in non-fermentative carbon sources. PASK is also important for proper regulation of glucose metabolism in mammals at both the hormonal and cellular level. In cultured pancreatic beta-cells, PASK is activated by elevated glucose concentrations and is required for glucose-stimulated transcription of the insulin gene. PASK knockdown in cultured myoblasts causes increased glucose oxidation and elevated cellular ATP levels. Mice lacking PASK exhibit increased metabolic rate and resistance to diet-induced obesity. Interestingly, PGC-1 expression and AMPK and TOR activity were not affected in PASK deficient mice, suggesting PASK may exert its metabolic effects through a new mechanism. We propose that PASK plays a significant role in nutrient sensing, metabolic regulation, and energy homeostasis, and is a potential therapeutic target for metabolic disease.
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PMID:The role of PAS kinase in regulating energy metabolism. 1834 4

We report a case of nail candidiasis with severe deformities. The patient was a 71-year-old woman who initially consulted our department on April 5, 2006. She had diabetes, chronic rheumatoid arthritis and multiple liver metastasis of unknown origin. She had taken prednisolone for treatment of chronic rheumatoid arthritis for a long period. The initial examination demonstrated deformation of 1/3 of the inner part of the nail plate in both the third and fourth fingers, with apparent hyperkeratosis under the deformed nail plates. KOH-prepared direct microscopy revealed the presence of numerous spores and pseudohyphae. Numerous fungal elements were detected by Grocott staining and PAS staining. Candida albicans was isolated and identified by cultivation on the ATG agar and PCR-RFLP. Fluconazole (100 mg/day) was administered from April 8, 2006. After 14 weeks of treatment her clinical findings had improved, however she died of multiple organ failure on July 25, 2006.
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PMID:[A case of nail candidiasis with severe deformities treated with oral fluconazole]. 1868 73

Diabetic nephropathy is a major microangiopathic complication of diabetes mellitus. Its features are represented by: proteinuria and renal function decrease. The etiology of proteinuria in diabetic patients is assessed in this study. The study was performed on 30 patients with diabetes mellitus (11 type 1, 19 type 2) and proteinuria (19 males and 11 females), at the mean age of 42.1+/-7.72 years. Renal biopsies were done with Vim-Silverman needle, using hematoxylin-eosin and PAS staining. Diabetic retinopathy was found in 26 patients (86.66%). The values of proteinuria were: 0.62+/-0.07 g/24 hours in 4 (13.33%), 2.41+/-1.26 g/24 hours in 10 (33.33%) and 4.68+/-2.11 g/24 hours in 16 patients (53.33%). 18 patients presented elevated blood pressure (170.11+/-6.25/97.12+/-4.44 mmHg). Reduced creatinine clearance (48.01+/-7.25 ml/min) was found in 7 patients (23.33%). Histological analysis showed: diffuse diabetic glomerular lesions in 14 patients (46.66%), nodular diabetic glomerular lesions associated with diffuse glomerular lesions in 12 patients (40%) and membranous glomerulonephritis, without diabetic lesions in 4 patients (13.33%). Appearance of proteinuria in diabetic patients is not synonymous with diabetic nephropathy, requiring further investigations. including renal biopsy.
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PMID:The etiology of proteinuria in diabetic patients. 1892 63

Granular cell astrocytoma (GCA) is an uncommon type of granular cell tumours (GCTs) in the central nervous system. Granular cells in these tumours are of enigmatic origin. We report a case of cerebral GCA in a 59-year-old man who suffered from diabetes and Addison-Biermer disease. The tumour was localized in the left parietal lobe. Microscopically, the tumour was almost entirely composed of large, polygonal cells with round to oval, granular eosinophilic, PAS-positive cytoplasm. The nuclei were located centrally or eccentrically and sometimes exhibited nucleolar vacuoles. The tumour cells were arranged in nests surrounded by blood vessels and connective tissue. Immunohistochemically, the granular tumour cells were reactive for GFAP and vimentin. They were intensively stained for ubiquitin and some of them were reactive for CD68. Moreover, a lot of stromal cells expressed CD68 reactivity. Ultrastructurally, most tumour cells were round or oval with only a few or without filaments. Their cytoplasm was filled with electron-dense granular material limited by a single membrane and autophagic vacuoles. Another type of tumour cells, present in a significantly lower number, revealed abundant cytoplasm with numerous intermediate filaments, swollen rough endoplasmic reticulum, mitochondria and a few clusters of granular material. Cells with numerous condensed electron-dense, bizarrely-shaped mitochondria and few filaments were occasionally observed. Among granular cells, macrophages with vacuoles and/or lamellar structures were visible. In our case, both immunohistochemical and ultrastructural analysis supported astroglial origin of the granular cell tumour.
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PMID:Granular cell astrocytoma. A case report with immunohistochemical and ultrastructural characterization. 1916 70

The inability to coordinate cellular metabolic processes with the cellular and organismal nutrient environment leads to a variety of disorders, including diabetes and obesity. Nutrient-sensing protein kinases, such as AMPK and mTOR, play a pivotal role in metabolic regulation and are promising therapeutic targets for the treatment of disease. In this Extra View, we describe another member of the nutrient-sensing protein kinase group, PAS kinase, which plays a role in the regulation of glucose utilization in both mammals and yeast. PAS kinase deficient mice are resistant to high fat diet-induced weight gain, insulin resistance and hepatic triglyceride hyperaccumulation, suggesting a role for PAS kinase in the regulation of glucose and lipid metabolism in mammals. Likewise, PAS kinase deficient yeast display altered glucose partitioning, favoring glycogen biosynthesis at the expense of cell wall biosynthesis. As a result, PAS kinase deficient yeast are sensitive to cell wall perturbing agents. This partitioning of glucose in response to PAS kinase activation is due to phosphorylation of Ugp1, the enzyme primarily responsible for UDP-glucose production. The two yeast PAS kinase homologs, Psk1 and Psk2, are activated by two stimuli, cell integrity stress and nonfermentative carbon sources. We review what is known about yeast PAS kinase and describe a genetic screen that may help elucidate pathways involved in PAS kinase activation and function.
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PMID:Regulation and function of yeast PAS kinase: a role in the maintenance of cellular integrity. 1944 50

Renal protection against diabetes-induced pathogenic injuries by multiple exposures to low-dose radiation (LDR) was investigated to develop a novel approach to the prevention of renal disease for diabetic subjects. C57BL/6J mice were given multiple low-dose streptozotocin (STZ; 6 x 60 [corrected] mg/kg) to produce a type 1 diabetes. Two weeks after diabetes onset, some of diabetic mice and age-matched nondiabetic mice were exposed whole body to 25 mGy X-rays every other day for 2, 4, 8, 12, and 16 wk. Diabetes caused a significant renal dysfunction, shown by time-dependent increase in urinary microalbumin (Malb) and decrease in urinary creatinine (Cre), and pathological changes, shown by significant increases in renal structural changes and PAS-positive staining. However, diabetes-induced renal dysfunction and pathological changes were significantly, albeit partially, attenuated by multiple exposures to LDR. Furthermore, LDR protection against diabetes-induced renal dysfunction and pathological changes was associated with a significant suppression of diabetes-increased systemic and renal inflammation, shown by significant increases in serum and renal TNFalpha, ICAM-1, IL-18, MCP-1, and PAI-1 contents. To further explore the mechanism by which LDR prevents diabetes-induced renal pathological changes, renal oxidative damage was examined by Western blotting and immunohistochemical staining for 3-nitrotyrosine and 4-hydroxynonenal. Significant increase in oxidative damage was observed in diabetic mice, but not diabetic mice, with LDR. Renal fibrosis, examined by Western blotting of connective tissue growth factor and Masson's trichrome staining, was also evident in the kidneys of diabetic mice but not diabetic mice with LDR. These results suggest that multiple exposures to LDR significantly suppress diabetes-induced systemic and renal inflammatory response and renal oxidative damage, resulting in a prevention of the renal dysfunction and fibrosis.
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PMID:Attenuation of diabetes-induced renal dysfunction by multiple exposures to low-dose radiation is associated with the suppression of systemic and renal inflammation. 2054 44

Renal disease is a common complication of diabetes mellitus. The pathogenesis of diabetic nephropathy is not well understood, but hyperglycemia seems to be a crucial factor. Recent evidence indicates that the overproduction of reactive oxygen species, observed in both clinical and experimental diabetes, and mitochondrial dysfunction are key factors in pathogenic process. The objective of this investigation was to test the hypothesis of whether hyperglycemia could affect kidney morphology and mitochondrial bioenergetics as well as susceptibility to oxidative stress in 12-month-old diabetic Goto-Kakizaki (GK) rats, a model of type 2 diabetes mellitus. We observed that there were no significant differences in the kidney respiratory function and phosphorylation capacity between GK and age-matched control Wistar rats. Mitochondria from kidneys of diabetic rats were equally susceptible to in vitro oxidative damage as those from normal rats, while coenzyme Q and alpha -tocopherol concentrations were similar in both types of preparations. However, the kidney of GK rats presented in most glomerulus a capillary basement membrane thickening with mesangial widening, in evolution to segmental glomerular sclerosis, and, in some interlobular arteries, excessive deposition of PAS-positive material at the tunica intima. The results show that the mild prolonged hyperglycemia and the kidney structural changes observed in GK rats are not sufficient to cause renal dysfunction and were not associated with functional and biochemical alterations in mitochondria.
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PMID:Mitochondrial function is not affected by renal morphological changes in diabetic goto-kakizaki rat. 2002 Oct 90


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